The first objective of this proposal is to continue our studies in the chemical induction of differentiaton of cultured human colon carcinoma cells to more normal or benign cell types. N,N-dimethylformamide (DMF) and soidum butyrate will contiue to be used because we an others have shown that these two agents induce alterations in the malignant phenotype of, and cancer maturational changes in, human colon carcinoma and other cancer cell types. The effect of retinoic acid on colon cancer cells will be assessed; this compound has not been previously studied in our laboratory. A specific aim of the tissue culture work will be to determine whether differentiation-inducing compounds can sensitize cultured human colon cells to X-irradiation or hyperthermia. The second objective of this proposal is to determine whether inducers can cause inhibitions in the growth of human colon carcinoma xenografts in nude mice, and whether there is any evidence of maturational effects accompanying growth inhibition of the solid tumors. A specific aim of the animal studies will be to determine whether DMF treatment of nude mice bearing human colon tumor xenografts will selectively sensitize the tumor to subsequent X-irradiation therapy. The experiments in which cultured colon cancer cells or xenogragt tumors are exposed to an inducer and are then treated with X-rays (or heat) are designed to address the following important question. Will the most effective use of differentiation-inducing agents, or biological modifiers, be in combination with conventional therapies in combined modality treatments? The work proposed in this application will hopefully help provide an answer to that question, as well as continue to provide basic information on the relationship between colon cancer and differentiation.